Acceleration of autologous in vivo recellularization of decellularized aortic conduits by fibronectin surface coating
Acceleration of autologous in vivo recellularization of decellularized aortic conduits by fibronectin surface coating
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DOI：
10.1016/j.biomaterials.2013.04.037
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发表时间：
2013-08-01
期刊：
影响因子：
14
通讯作者：
Akhyari, Payam
中科院分区：
文献类型：
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作者：
Assmann, Alexander;Delfs, Christofer;Akhyari, Payam
脱细胞是一种有希望的选择，以减少对供体移植物的免疫和炎症反应。为了加速主动脉导管的自体体内再细胞化以增强生物相容性，我们在标准化大鼠植入模型中测试了纤连蛋白表面涂层。用共价Alexa 488标记的纤连蛋白（50 μ g/ml，24小时）对去污剂脱细胞的大鼠主动脉导管（n = 36）进行表面涂覆，并植入Wistar大鼠的体循环中长达8周（FN组; n = 18）。无涂层种植体作为对照（C组; n = 18）。在主动脉导管的两个表面上的纤连蛋白结合的荧光持续至少8周。通过组织学和免疫荧光检查细胞再增殖（n = 24）。FN组管腔内皮化显著加速（8周后p = 0.006），然而，局部肌成纤维细胞增生伴内膜与中膜厚度比值显著增加（8周后p = 0.0002）。与C组相比，源自外膜表面的α-平滑肌肌动蛋白和结蛋白阳性细胞侵入纤连蛋白涂覆的导管的介质中显著增加（p < 0.0001）。在这些内侧区域，原位酶谱显示基质金属蛋白酶活性增强。在两组中，炎症细胞标志物（CD 3和CD 68）和血栓形成的迹象被证明是阴性的。关于细胞粘附、炎症和钙化的几种标志物，定量实时PCR（n = 12）显示没有显著的组间差异。脱细胞心血管植入物的纤连蛋白表面涂层被证明是可行的，并在体循环中持续至少8周。生物功能蛋白涂层加速自体体内内皮化，并诱导中膜再细胞化显著增加。因此，这一策略可能有助于改善目前临床应用的生物瓣膜。(C)2013爱思唯尔有限公司保留所有权利。
Decellularization is a promising option to diminish immune and inflammatory response against donor grafts. In order to accelerate the autologous in vivo recellularization of aortic conduits for an enhanced biocompatibility, we tested fibronectin surface coating in a standardized rat implantation model. Detergent-decellularized rat aortic conduits (n = 36) were surface-coated with covalently Alexa488-labeled fibronectin (50 mu g/ml, 24 h) and implanted into the systemic circulation of Wistar rats for up to 8 weeks (group FN; n = 18). Uncoated implants served as controls (group C; n = 18). Fibronectin-bound fluorescence on both surfaces of the aortic conduits was persistent for at least 8 weeks. Cellular repopulation was examined by histology and immunofluorescence (n = 24). Luminal endothelialization was significantly accelerated in group FN (p = 0.006 after 8 weeks), however, local myofibroblast hyperplasia with significantly increased ratio of intima-to-media thickness occurred (p = 0.0002 after 8 weeks). Originating from the adventitial surface, alpha-smooth muscle actin and desmin positive cell invasion into the media of fibronectin-coated conduits was significantly increased as compared to group C (p < 0.0001). In these medial areas, in situ zymography revealed enhanced matrix metalloproteinase activity. In both groups, inflammatory cell markers (CD3 and CD68) and signs of thrombosis proved negative. With regard to several markers of cell adhesion, inflammation and calcification, quantitative real-time PCR (n = 12) revealed no significant inter-group differences. Fibronectin surface coating of decellularized cardiovascular implants proved feasible and persistent for at least 8 weeks in the systemic circulation. Biofunctional protein coating accelerated the autologous in vivo endothelialization and induced a significantly increased medial recellularization. Therefore, this strategy may contribute to the improvement of current clinically applied bioprostheses. (C) 2013 Elsevier Ltd. All rights reserved.